Anti-plaque toothpaste

ABSTRACT

Toothpastes which contain 10-60 wt. % of polishing agents, 2-20 wt. % of humectants, 0.5-5 wt. % of water-soluble consistency regulators and 0.05-0.5 wt. % of antimicrobial biguanides, as well as 1-5 wt. % of other additives from the group of surface-active substances, aromatic oils, and sweeteners, have a particularly high biguanide availability if the polishing agent consists mainly of calcium carbonate, the consistency regulators are non-ionic polysaccharide derivatives and the surface-active substances are cationic surfactants with a linear alkyl group containing 12-18 carbon atoms and one or two tertiary amino groups or quaternary ammonium groups. Optionally a non-ionogenic solubilizer for the aromatic oil may also be present in the toothpastes.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a toothpaste in the form of a dispersion ofcalcium carbonate as polish in an aqueous carrier which contains anantimicrobial biguanide compound as plaque-inhibiting component and ofwhich the other components are selected according to type and quantityso that plaque formation is optimally inhibited despite a relatively lowdosage of the antimicrobial biguanide compound.

2. Statement of Related Art

It has long been known that antimicrobial biguanide compounds areeffective in preventing the formation of dental plaque. However, theireffect is greatly reduced or even completely eliminated by many of thecomponents typically used in toothpastes, more particularly by certainpolishes, such as calcium carbonate for example, and also by manybinders and viscosity regulators, surfactants and even by certainsweeteners. Accordingly, there has been no shortage of attempts to findcomponents which do not impair antimicrobial biguanides or which preventany such impairment. Thus, according to DE-OS 21 58 149 for example,α-aluminum oxide trihydrate having a certain particle size is used asthe polish component. On the other hand, according to DE-OS 34 44 958,certain surfactants enhance the effect of antimicrobial biguanide.However, this effect also is disturbed in the presence of calciumcarbonate as polish or in the presence of anionic binders and viscosityregulators, anionic surfactants and solubilizers.

DESCRIPTION OF THE INVENTION Summary of the Invention

Accordingly, a satisfactory toothpaste which is extremely effective ininhibiting plaque formation, even despite low doses of the antimicrobialbiguanide compounds, is not known from the prior art. The problemaddressed by the present invention was to solve this problem fortoothpastes containing chalk as the polish component. The presentinvention relates to a toothpaste in the form of an aqueous dispersioncontaining 10 to 60% by weight of polish, 2 to 20% by weight ofhumectants, 0.5 to 5% by weight of water-soluble viscosity regulators,0.05 to 0.5% by weight of antimicrobial biguanides and 1 to 5% by weightof other additives from the group of surfactants, flavoring oils andsweeteners, characterized in that calcium carbon-ate (chalk) ispredominantly present as the polish, non-ionic polysaccharidederivatives are present as the viscosity regulators and a cationicsurfactant containing a linear C₁₂₋₁₈ alkyl group and one or twotertiary amino groups or quaternary ammonium groups are present as thesurfactants, a nonionic solubilizer for the flavoring oil optionallybeing present.

DESCRIPTION OF PREFERRED EMBODIMENTS

The polish used is preferably a precipitated chalk of which theparticles are essentially smaller than 20 μm in diameter, better yetsmaller than 10 μm and preferably between 1 and 5 μm.

Suitable humectants are glycerol, sorbitol, propylene glycol andpolyethylene glycols, glycerol and/or sorbitol being preferred. Suitablewater-soluble viscosity regulators are nonionic polysaccharidederivatives, for example methyl, hydroxyethyl and hydroxypropyl ethersof cellulose, starch, guar, xanthan and vegetable gums. Hydroxyethylcellulose and methyl hydroxypropyl cellulose are preferably used.

The 1,1'-hexamethylene-bis-{5-(4-chlorophenyl)-biguanide}("chlorhexidine") known from GB-A-705,838 in the form of awater-soluble, physiologically acceptable salt, for example in the formof the acetate or gluoonate, is used as the antimicrobial biguanidecompound. Other antimicrobial biguanide compounds suitable for thepurposes of the invention are, for example,1,1'-hexamethylene-bis-{5-(4-fluorophenyl)-biguanide} ("fluorhexidine"),the polyhexamethylene biguanide compounds of the Vantocil IB (ICI) typeknown from GB-A-702,268 and the antimicrobial biguanide compounds knownfrom U.S. Pat. Nos. 2,684,924, 2,990,425, 3,468,898, 4,022,834,4,053,636 and 4,198,392.

Preferred cationic surfactants in the toothpaste according to theinvention are those corresponding to general formula I ##STR1## in whichR¹ is a C₁₂₋₂₀ alkyl or hydroxyalkyl group, R² and R³ represent a C₁₋₄alkyl group or a C₂₋₄ 2-hydroxyalkyl group, R⁴ is hydrogen, a C₁₋₄ alkylgroup, a benzyl group or a C₂₋₄ 2-hydroxyalkyl group, R⁵ is a C₁₋₄alkylene group, x =0 or 1 and A.sup.(-) is a fluoride, chloride,bromide, methoxy-sulfate or ethoxysulfate anion. These cationicsurfactants are present in a quantity of 0.01 to 1% by weight.Particularly suitable cationic surfactants corresponding to formula Iare, for example, cetyl trimethyl ammonium chloride, lauryl dimethylbenzyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride,2-hydroxydodecyl-2-hydroxyethyl dimethyl ammonium chloride,N-octadecyl-N,N',N'-tris-(2-hydroxyethyl)-1,3-diaminopropanedihydrochloride (amine fluoride).

The addition of the cationic surfactants corresponding to generalformula I to the toothpaste according to the invention significantlyreduces the sorption of the antimicrobial, plaque-inhibiting biguanidecompounds on the polish, so that the biguanide compound remains freelyavailable in the toothpaste and fully available for preventing plaque.By addition of the cationic surfactants according to the invention, itis possible to produce plaque-inhibiting toothpastes containing calciumcarbonate a the polish. Increasing the freely available chlorhexidine ina chalk dispersion containing 0.1% by weight chlorhexidine by additionof the cationic surfactants is demonstrated in Example 1.

The toothpaste according to the invention can be improved in itsorganoleptic properties by addition of flavoring oils and sweeteners.Suitable flavoring oils are any of the natural and synthetic flavoringstypically used for oral and dental care preparations. Natural flavoringsmay be used both in the form of the ethereal oils isolated from thedrugs and in the form of the individual components isolated therefrom.The toothpaste according to the invention should preferably contain atleast one flavoring oil from the group consisting of peppermint oil,spearmint oil, aniseed oil, Japanese anise oil, caraway oil, eucalyptusoil, fennel oil, cinnamon oil, clove oil, geranium oil, sage oil,pimento oil, thyme oil, majoram oil, basil oil, citrus oil, gaultheriaoil or one or more components of these oils either isolated therefrom orsynthetically produced. The most important components of the oilsmentioned are, for example, menthol, carvone, anethol, cineol, eugenol,cinnamaldehyde, caryophyllene, geraniol, citronellol, linalool, salvene,thymol, terpinene, terpineol, methyl chavicol and methyl salicylate.Other suitable flavorings are, for example, menthyl acetate, vanillin,ionone, linalyl acetate, rhodinol and piperitone.

According to the invention, a nonionic solubilizer is required forsolubilizing these generally water-insoluble flavoring oils in thetoothpaste. Suitable solubilizers belong to the group of surface-activecompounds. Accordingly, the present invention relates to a toothpasteaccording to the invention containing 0.1 to 0.5% by weight of aflavoring oil and 0.1 to 0.7% by weight of a nonionic solubilizer,preferably from the group of ethoxylated fatty acid glycerides,ethoxylated fatty acid sorbitan partial esters, or fatty acid partialesters of glycerol and sorbitan ethoxylates.

Solubilizers from the group of ethoxylated fatty acid glyceridesinclude, above all, adducts of approximately 20 to 60 moles of ethyleneoxide with mono- and diglycerides of linear C₁₂₋₁₈ fatty acids or withtriglycerides of hydroxy fatty acids, such as hydroxystearic acid orricinoleic acid. Other suitable solubilizers are ethoxylated fatty acidsorbitan partial esters, i.e. preferably adducts of 20 to 60 moles ofethylene oxide with sorbitan monoesters and sorbitan diesters of C₁₂₋₁₈fatty acids. Other suitable solubilizers are fatty acid partial estersof glycerol and sorbitan ethoxylates, i.e. preferably mono- anddi-esters of C₁₂₋₁₈ fatty acids and adducts of 20 to 60 moles ofethylene oxide with 1 mole of glycerol or 1 mole of sorbitol.

The toothpaste according to the invention preferably contains adducts of20 to 60 moles of ethylene oxide with hydrogenated or non-hydrogenatedcastor oil (i.e. with hydroxystearic acid or ricinoleic acidtriglyceride), with glycerol mono- and/or di-stearate, or with sorbitanmono- and/or di-stearate as solubilizers for any flavoring oils present.

Suitable sweeteners are either natural sugars, for example sucrose,maltose, lactose and fructose, or synthetic sweeteners, but preferablynonionic or amphoteric substances. The preferred sweetener isL-aspartyl-L-phenyl alanine methyl ester commercially available asAspartame®.

Other known toothpaste additives may also be present in small quantitiesof, in all, up to at most 3% by weight providing they are compatiblewith the antimicrobial biguanide and do not impair its effect. Suchadditives are, for example, caries inhibitors, such as sodium fluorideor sodium monofluorophosphate, pigments, such as titanium dioxide forexample dyes, pH regulators and buffers, for example citric acid andsalts thereof or phosphoric acid and alkali metal salts thereof, andwound-healing and anti-inflammatory agents, such as for exampleallantoin, urea, azulene or camomile-based active substances.

The following Examples are intended to illustrate the invention withoutlimiting it in any way.

EXAMPLES 1. Testing of the Increase in the Content of Freely AvailableAnalytically Detectable Chlorhexidine After Addition of CationicSurfactant

A standard dispersion of 40% by weight chalk (calcium carbonate) and0.1% by weight chlorhexidine in water was prepared and increasingquantities of cationic surfactants were added. After addition of thecationic surfactant, the dispersions were shaken for 24 hours toestablish the equilibrium position at 20° C. The dispersions were thendiluted with 3 parts by weight of water per part by weight ofdispersion, filtered off from the calcium carbonate and tested for thefree chlorhexidine content in the clear filtrate. The free chlorhexidinewas analytically determined by the method described by Cropper, Plattand Puttnam in J. Soc. Cosmet. Chem. 26, (1975), pages 355-373.

The following cationic surfactants were used:

A: Cetyl trimethyl ammonium bromide

B: 2-Hydroxydodecyl-2-hydroxyethyl dimethyl ammonium chloride

C: N-octadecyl-N,N',N'-tris-(2-hydroxyethyl)-1,3-diaminopropanedihydrofluoride (so-called amine fluoride).

The type and concentration of cationic surfactant added and the quantityof freely available chlorhexidine, after 24 hours of equilibration, in %of the quantity added are shown in the following Table.

    __________________________________________________________________________                  Example No.                                                                   1 2  3  4  5  6  7  8  9  10 11 12                              __________________________________________________________________________    Cation. surfactant                                                                          --                                                                              A  A  A  A  B  B  B  B  C  C  C                               Concentration % by weight                                                                   --                                                                              0.01                                                                             0.05                                                                             0.1                                                                              0.5                                                                              0.01                                                                             0.05                                                                             0.1                                                                              0.5                                                                              0.17                                                                             0.33                                                                             0.66                            Free chlorhexidine in %                                                                     15                                                                              15 27 64 90 20 20 20 33 20 20 85                              __________________________________________________________________________

2. Toothpaste According to the Invention

    ______________________________________                                        Formulation:                                                                  ______________________________________                                        Chalk (precipitated calcium carbonate)                                                              40.0% by weight                                         Sorbitol (70% solution)                                                                             5.0% by weight                                          Glycerol              5.0% by weight                                          Methyl hydroxypropyl cellulose.sup.1)                                                               2.5% by weight                                          Hydroxyethyl cellulose.sup.2)                                                                       1.3% by weight                                          Cation. surfactant C (amine fluoride)                                                               1.0% by weight                                          Peppermint flavoring oil                                                                            0.3% by weight                                          HR 60.sup.3)          0.3% by weight                                          Chlorhexidine digluconate                                                                           0.2% by weight                                          Aspartame ®       0.01% by weight                                         Water                 ad 100% by weight                                       ______________________________________                                         .sup.1) The commercial product Culminal MHPC 100 (Henkel KGaA) was used.      .sup.2) The commercial product Cellobond HEC (BP) was used.                   .sup.3) Adduct of 60 moles of ethylene oxide with hydrogenated castor oil                                                                              

What is claimed is:
 1. A toothpaste in the form of an aqueous dispersion containing 10.0 to 60.0% by weight of polishes, 2.0 to 20.0% by weight of humectants, 0.5 to 5.0% by weight of water-soluble viscosity regulators, 0.05 to 0.5% by weight of antimicrobial biguanides, and 1.0 to 5.0% by weight of other additives from the group of surfactants, flavoring oils, and sweeteners, wherein the improvement is that calcium carbonate is predominantly present as the polish, non-ionic polysaccharide derivatives are present as the viscosity regulators, and a cationic surfactant containing a linear C₁₂ -alkyl group and one or two tertiary amino groups or quaternary ammonium groups is present as the surfactant, a nonionic solubilizer for the flavoring oil optionally being present.
 2. A toothpaste as claimed in claim 1, wherein 1,1'-hexamethylene-bis-(4-chlorophenyl)-biguanide (chlorhexidine) in the form of a water-soluble salt is present as the antimicrobial biguanide.
 3. A toothpaste as claimed in claim 2, wherein a cationic surfactant corresponding to formula (I) ##STR2## in which R¹ is a C₁₂₋₂₀ alkyl or hydroxyalkyl group; R² and R³ represent a C₁₋₄ alkyl group or a C₂₋₄ 2-hydroxyalkyl group; R⁴ is hydrogen, a C₁₋₄ alkyl group, a benzyl group, or a C₂₋₄ 2-hydroxyalkyl group; R⁵ is a C₁₋₄ alkylene group; x=0 or 1; and A.sup.(-) is a fluoride, chloride, bromide, methoxysulfate, or ethoxysulfate anion, is present as the cationic surfactant in a quantity of 0.01 to 1% by weight.
 4. A toothpaste as claimed in claim 3, which contains 0.1 to 0.5% by weight of a flavoring oil and 0.1 to 0.7% by weight of a solubilizer from the group of ethoxylated fatty acid glycerides, ethoxylated fatty acid sorbitan partial esters or fatty acid partial esters of glycerol or sorbitan ethoxylates.
 5. A toothpaste as claimed in claim 4, wherein an adduct of 20 to 60 moles of ethylene oxide with a material selected from the group consisting of hydrogenated and non-hydrogenated castor oil, glycerol mono- and di-stearate and mixtures of mono- and di-stearate, and sorbitan mono- and di-stearate and mixtures of mono- and di-stearate is present as the solubilizer for the flavoring oil.
 6. A toothpaste as claimed in claim 1, wherein a cationic surfactant corresponding to formula (I) ##STR3## in which R¹ is a C₁₂₋₂₀ alkyl or hydroxyalkyl group; R² and R³ represent a C₁₋₄ alkyl group or a C₂₋₄ 2-hydroxyalkyl group; R⁴ is hydrogen, a C₁₋₄ alkyl group, a benzyl group, or a C₂₋₄ 2-hydroxyalkyl group; R⁵ is a C₁₋₄ alkylene group; x=0 or 1; and A.sup.(-) is a fluoride, chloride, bromide, methoxysulfate, or ethoxysulfate anion, is present as the cationic surfactant in a quantity of 0.01 to 1% by weight.
 7. A toothpaste as claimed in claim 6, which contains 0.1 to 0.5% by weight of a flavoring oil and 0.1 to 0.7% by weight of a solubilizer from the group of ethoxylated fatty acid glycerides, ethoxylated fatty acid sorbitan partial esters, or fatty acid partial esters of glycerol or sorbitan ethoxylates.
 8. A toothpaste as claimed in claim 2, which contains 0.1 to 0.5% by weight of a flavoring oil and 0.1 to 0.7% by weight of a solubilizer from the group of ethoxylated fatty acid glycerides, ethoxylated fatty acid sorbitan partial esters, or fatty acid partial esters of glycerol or sorbitan ethoxylates.
 9. A toothpaste as claimed in claim 1, which contains 0.1 to 0.5% by weight of a flavoring oil and 0.1 to 0.7% by weight of a solubilizer from the group of ethoxylated fatty acid glycerides, ethoxylated fatty acid sorbitan partial esters, or fatty acid partial esters of glycerol or sorbitan ethoxylates.
 10. A toothpaste as claimed in claim 9, wherein an adduct of 20 to 60 moles of ethylene oxide with a material selected from the group consisting of hydrogenated and non-hydrogenated castor oil, glycerol mono- and di-stearate and mixtures of mono- and di-stearate, and sorbitan mono- and di-stearate and mixtures of mono- and di-stearate is present as the solubilizer for the flavoring oil.
 11. A toothpaste as claimed in claim 8, wherein an adduct of 20 to 60 moles of ethylene oxide with a material selected from the group consisting of hydrogenated and non-hydrogenated castor oil, glycerol mono- and di-stearate and mixtures of mono- and di-stearate, and sorbitan mono- and di-stearate and mixtures of mono- and di-stearate is present as the solubilizer for the flavoring oil.
 12. A toothpaste as claimed in claim 7, wherein an adduct of 20 to 60 moles of ethylene oxide with a material selected from the group consisting of hydrogenated and non-hydrogenated castor oil, glycerol mono- and di-stearate and mixtures of mono- and di-stearate, and sorbitan mono- and di-stearate and mixtures of mono- and di-stearate is present as the solubilizer for the flavoring oil.
 13. A toothpaste as claimed in claim 6, wherein an adduct of 20 to 60 moles of ethylene oxide with a material selected from the group consisting of hydrogenated and non-hydrogenated castor oil, glycerol mono- and di-stearate and mixtures of mono- and di-stearate, and sorbitan mono- and di-stearate and mixtures of mono- and di-stearate is present as the solubilizer for the flavoring oil.
 14. A toothpaste as claimed in claim 3, wherein an adduct of 20 to 60 moles of ethylene oxide with a material selected from the group consisting of hydrogenated and non-hydrogenated castor oil, glycerol mono- and di-stearate and mixtures of mono- and di-stearate, and sorbitan mono- and di-stearate and mixtures of mono- and di-stearate is present as the solubilizer for the flavoring oil.
 15. A toothpaste as claimed in claim 2, wherein an adduct of 20 to 60 moles of ethylene oxide with a material selected from the group consisting of hydrogenated and non-hydrogenated castor oil, glycerol mono- and di-stearate and mixtures of mono- and di-stearate, and sorbitan mono- and di-stearate and mixtures of mono- and di-stearate is present as the solubilizer for the flavoring oil.
 16. A toothpaste as claimed in claim 1, wherein an adduct of 20 to 60 moles of ethylene oxide with a material selected from the group consisting of hydrogenated and non-hydrogenated castor oil, glycerol mono- and di-stearate and mixtures of mono- and di-stearate, and sorbitan mono- and di-stearate and mixtures of mono- and di-stearate is present as the solubilizer for the flavoring oil. 